Synergistic pesticidal compositions and related methods

ABSTRACT

A pesticidal composition comprises a synergistically effective amount of a chloride channel activator compound and a pesticide selected from N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-((3,3,3 -trifluoropropyl)thio) propanamide (I), N-(3-chloro-1-(pyridine-3-yl)-1H-pyrazol-4-yl)-N-ethyl-((3,3,3,3-trifluoropropyl) sulfinyl)propanamide (II), or any agriculturally acceptable salt thereof. A method of controlling pests comprises applying the pesticidal composition near a population of pests. A method of protecting a plant from infestation and attack by pests comprises contacting the plant with the synergistic pesticidal composition.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of the filing date of U.S.Provisional Patent Application Ser. No. 61/894,167, filed Oct. 22, 2013,for “SYNERGISTIC PESTICIDAL COMPOSITIONS AND RELATED METHODS,” pending,the disclosure of which is hereby incorporated herein in its entirety bythis reference.

TECHNICAL FIELD

This disclosure relates to the field of compounds having pesticidalutility against pests in Phyla Nematoda, Arthropoda, and/or Mollusca,processes to produce such compounds and intermediates used in suchprocesses. These compounds may be used, for example, as nematicides,acaricides, miticides, and/or molluscicides.

BACKGROUND

Controlling pest populations is essential to human health, modernagriculture, food storage, and hygiene. There are more than ten thousandspecies of pests that cause losses in agriculture and the worldwideagricultural losses amount to billions of U.S. dollars each year.Accordingly, there exists a continuous need for new pesticides and formethods of producing and using such pesticides.

The Insecticide Resistance Action Committee (IRAC) has classifiedinsecticides into categories based on the best available evidence of themode of action of such insecticides. Insecticides in the IRAC Mode ofAction Group 6 are chloride channel activators. The insecticides in thisclass are believed to allosterically activate glutamate-gated chloridechannels (GluCls), causing paralysis of the affected insects. Glutamatehas been reported an important inhibitory neurotransmitter in insects.The insecticides in this class may be avermectins-based compounds ormilbemycins-based compounds. Examples of these insecticides may includeabamectin, emamectin benzoate, lepimectin, or milbemectin.

Emamectin benzoate is a 4′-deoxy-4′-methyl-amino benzoate salt ofavermectin B1 (abamectin). Abamectin is a mixture of avermectinscontaining more than 80% of avermectin B1a, which is(10E,14E,16E)-(1R,4S,5′S,6S,6′R,8R,12S,13S,20R,21R,24S)-6′-[(S)-sec-butyl]-21,24-dihydroxy-5′,11,13,22-tetramethyl-2-oxo-(3,7,19-trioxatetracyclo[15.6.1.1^(4,8).0^(20,24,)]pentacosa-10,14,16,22-tetraene)-6-spiro-2′-(5′,6′-dihydro-2′H-pyran)-12-yl2,6-dideoxy-3-O-methyl-4-O-(2,4,6-trideoxy-3-O-methyl-4-methylamino-α-L-lyxo-hexapyranosyl)-α-L-arabino-hexapyranoside,and less than 20% of avermectin B1b, which is(10E,14E,16E)-(1R,4S,5′S,6S,6′R,8R,12S,13S,20R,21R,24S)-21,24-dihydroxy-6′-isopropyl-5′,11,13,22-tetramethyl-2-oxo-(3,7,19-trioxatetracyclo[15.6.1.1^(4,8).0^(20,24)]pentacosa-10,14,16,22-tetraene)-6-spiro-2′-(5′,6′-dihydro-2′H-pyran)-12-yl-2,6-dideoxy-3-O-methyl-4-O-(2,4,6-trideoxy-3-O-methyl-4-methylamino-α-L-lyxo-hexapyranosyl)-α-L-arabino-hexapyranoside.

Although the rotational application of pesticides having different modesof action may be adopted for good pest management practice, thisapproach does not necessarily give satisfactory insect control.Furthermore, even though combinations of pesticides have been studied, ahigh synergistic action has not always been found.

DETAILED DESCRIPTION

As used herein, the term “synergistic effect” or grammatical variationsthereof means and includes a cooperative action encountered in acombination of two or more active compounds in which the combinedactivity of the two or more active compounds exceeds the sum of theactivity of each active compound alone.

The term “synergistically effective amount,” as used herein, means andincludes an amount of two or more active compounds that provides asynergistic effect defined above.

The term “pesticidally effective amount,” as used herein, means andincludes an amount of active pesticide that causes an adverse effect tothe at least one pest, wherein the adverse effect may include deviationsfrom natural development, killing, regulation, or the like.

As used herein, the term “control” or grammatical variations thereofmeans and includes regulating the number of living pests or regulatingthe number of viable eggs of the pests or both.

The term “chloride channel activator compound,” as used herein, meansand includes any insecticides that are classified by the InsecticideResistance Action Committee (IRAC), based on the best available evidenceof the mode of action, to be within the IRAC Mode of Action Group 6.

In one particular embodiment, a pesticidal composition comprises asynergistically effective amount of a chloride channel activatorcompound in combination with a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide(II), or any agriculturally acceptable salt thereof.

It is appreciated that a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide (I), N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide(II), or any agriculturally acceptable salt thereof may be oxidized tothe corresponding sulfone in the presence of oxygen.

As shown in the examples, the existence of synergistic effect isdetermined using the method described in Colby S. R., “CalculatingSynergistic and Antagonistic Responses of Herbicide Combinations,”Weeds, 1967, 15, 20-22.

Surprisingly, it has been found that the pesticidal composition of thepresent disclosure has superior pest control at lower levels of thecombined concentrations of the chloride channel activator compound andthe pesticide (I), (II), or any agriculturally acceptable salt thereofemployed than that which may be achieved when the chloride channelactivator compound and the pesticide (I), (II), or any agriculturallyacceptable salt thereof are applied alone. In other words, thesynergistic pesticidal composition is not a mere admixture of two activecompounds resulting in the aggregation of the properties of the activecompounds employed in the composition.

In some embodiments, the pesticidal compositions may comprise asynergistically effective amount of an avermectins-based compound incombination with a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide (II) or any agriculturally acceptable salt thereof.

In other embodiments, the pesticidal compositions may comprise asynergistically effective amount of a milbemycins-based compound incombination with a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide (II) or any agriculturally acceptable salt thereof.

In further embodiments, the pesticidal compositions may comprise asynergistically effective amount of a pesticide selected from (I), (II),or any agriculturally acceptable salt thereof in combination with atleast one of abamectin, emamectin benzoate, lepimectin, and milbemectin.

In still further embodiments, the pesticidal compositions may comprise asynergistically effective amount of emamectin benzoate in combinationwith a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide (I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide (II) or any agriculturally acceptable salt thereof.

TABLE 1A Range of the Weight Ratio of Pesticide I or II No. to ChlorideChannel Activator Compound 1 20:1 to 1:20 2 15:1 to 1:15 3 10:1 to 1:104 5:1 to 1:5 5 4:1 to 1:4 6 3:1 to 1:3 7 2:1 to 1:2 8 1:1

Table 1A shows weight ratios of the pesticide (I), (II), or anyagriculturally acceptable salt thereof to the chloride channel activatorcompound in the synergistic pesticidal compositions. In someembodiments, the weight ratio of the pesticide to the chloride channelactivator compound may be between about 20:1 and about 1:20. In someembodiments, the weight ratio of the pesticide to the chloride channelactivator compound may be between about 15:1 and about 1:15. In someembodiments, the weight ratio of the pesticide to the chloride channelactivator compound may be between about 10:1 and about 1:10. In someembodiments, the weight ratio of the pesticide to the chloride channelactivator compound may be between about 5:1 and about 1:5. In someembodiments, the weight ratio of the pesticide to the chloride channelactivator compound may be between about 4:1 and about 1:4. In someembodiments, the weight ratio of the pesticide to the chloride channelactivator compound may be between about 3:1 and about 1:3. In someembodiments, the weight ratio of the pesticide to the chloride channelactivator compound may be between about 2:1 and about 1:2. In someembodiments, the weight ratio of the pesticide to the chloride channelactivator compound may be about 1:1. Additionally, the weight ratiolimits of the pesticide to the chloride channel activator compound inthe aforementioned embodiments may be interchangeable. By way ofnon-limiting example, the weight ratio of the pesticide to the chloridechannel activator compound may be between about 1:3 and about 20:1.

TABLE 1B Chloride channel activator compound (Y) Parts by weight 20 X, YX, Y 15 X, Y X, Y X, Y 10 X,Y X, Y  5 X, Y X,Y X, Y X, Y  4 X, Y X, Y X,Y X, Y  3 X,Y X, Y X, Y X, Y X, Y X, Y  2 X, Y X, Y X, Y X, Y  1 X, Y X,Y X, Y X, Y X, Y X, Y X, Y X, Y 1 2 3 4 5 10 15 20 Pesticide (I or II)(X) Parts by weight

Weight ratios of the pesticide (I), (II), or any agriculturallyacceptable salt thereof to the chloride channel activator compoundenvisioned to be synergistic pesticidal compositions may be depicted asX:Y; wherein X is the parts by weight of the pesticide (I), (II), or anyagriculturally acceptable salt thereof, and Y is the parts by weight ofthe chloride channel activator compound. The numerical range of theparts by weight for X is 0<X≦20 and the parts by weight for Y is 0<Y≦20as shown graphically in table 1B. By way of non-limiting example, theweight ratio of the pesticide to the chloride channel activator compoundmay be about 20:1.

Ranges of weight ratios of the pesticide (I), (II), or anyagriculturally acceptable salt thereof to the chloride channel activatorcompound envisioned to be synergistic pesticidal compositions may bedepicted as X₁:Y₁ to X₂:Y₂, wherein X and Y are defined as above. In oneparticular embodiment, the range of weight ratios may be X₁:Y₁ to X₂:Y₂,wherein X₁>Y₁ and X₂<Y₂. By way of non-limiting example, the range ofweight ratios of the pesticide to the chloride channel activatorcompound may be between about 3:1 and about 1:3. In some embodiments,the range of weight ratios may be X₁:Y₁ to X₂:Y₂, wherein X₁>Y₁ andX₂>Y₂. By way of non-limiting example, the range of weight ratios of thepesticide to the chloride channel activator compound may be betweenabout 15:1 and about 3:1. In further embodiments, the range of weightratios may be X₁:Y₁ to X₂:Y₂, wherein X₁<Y₁ and X₂<Y₂. By way ofnon-limiting example, the range of weight ratios of the pesticide to thechloride channel activator compound may be between about 1:3 and about1:20.

Table 1C shows further weight ratios of the pesticide (I), (II), or anyagriculturally acceptable salt thereof to the chloride channel activatorcompound in the synergistic pesticidal compositions, according toparticular embodiments of present disclosure. In some particularembodiments, the weight ratio of the pesticide (I), (II), or anyagriculturally acceptable salt thereof to the chloride channel activatorcompound may be no more than about 2048:1. In further embodiments, theweight ratio of the pesticide to the chloride channel activator compoundmay be no more than about 256:1. In further embodiments, the weightratio of the pesticide to the chloride channel activator compound may beno more than about 64:1. In further embodiments, the weight ratio of thepesticide to the chloride channel activator compound may be no more thanabout 32:1. In yet further embodiments, the weight ratio of thepesticide to the chloride channel activator compound may be no more thanabout 16:1.

TABLE 1C Dose Rate Of Dose Rate of Chloride Weight Ratio of PesticidePesticide (I or II) Channel Activator (I or II) to Chloride Channel(weight %) Compound (weight %) Activator Compound 0.04 0.00002 ≦2048:1 0.04 0.000156 ≦256:1  0.0025 0.000039 ≦64:1 0.0025 0.000078 ≦32:10.000625 0.000039 ≦16:1

The weight ratio of the pesticide (I), (II), or any agriculturallyacceptable salt thereof to the chloride channel activator compound inthe synergistic pesticidal composition may be varied and different fromthose described in table 1A, table 1B, and table 1C. One skilled in theart recognizes that the synergistic effective amount of the combinationof active compounds may vary accordingly to various prevailingconditions. Non-limiting examples of such prevailing conditions mayinclude the type of pests, the type of crops, the mode of application,the application timing, the weather conditions, the soil conditions, thetopographical character, or the like. It is understood that one skilledin the art may readily determine the synergistic effective amount of thechloride channel activator compound and the pesticide (I), (II), or anyagriculturally acceptable salt thereof accordingly to the prevailingconditions.

In some embodiments, the pesticidal composition may comprise asynergistically effective amount of a chloride channel activatorcompound in combination with a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide (I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide (II), or any agriculturally acceptable saltthereof, and a phytologically-acceptable inert carrier (e.g., solidcarrier, or liquid carrier).

In further embodiments, the pesticidal composition may further compriseat least one additive selected from a surfactant, a stabilizer, anemetic agent, a disintegrating agent, an antifoaming agent, a wettingagent, a dispersing agent, a binding agent, dye, filler, or combinationsthereof.

In particular embodiments, each of the active compounds (a chloridechannel activator compound and a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3((3,3,3-trifluoropropyl)sulfinyl)propanamide(II), or any agriculturally acceptable salt thereof) may be formulatedseparately as a wettable powder, emulsifiable concentrate, aqueous orliquid flowable, suspension concentrate or any one of the conventionalformulations used for pesticides, and then tank-mixed in the field withwater or other liquid for application as a liquid spray mixture. Whendesired, the separately formulated pesticides may also be appliedsequentially.

In some embodiments, the synergistic pesticidal composition may beformulated into a more concentrated primary composition, which is thendiluted with water or other diluent before use. In such embodiments, thesynergistic pesticidal composition may further comprise a surface activeagent.

In one particular embodiment, the method of protecting a plant frominfestation and attack by pests comprises contacting the plant with apesticidal composition comprising a synergistically effective amount ofa chloride channel activator compound in combination with a pesticideselected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide(II), or any agriculturally acceptable salt thereof.

In some embodiments, the pesticidal compositions may be in the form ofsolid. Non-limiting examples of the solid forms may include powder, dustor granular formulations.

In other embodiments, the pesticidal compositions may be in the form ofliquid formulation. Examples of the liquid forms may include, but arenot limited to, dispersion, suspension, emulsion or solution inappropriate liquid carrier. In particular embodiments, the synergisticpesticidal compositions may be in the form of liquid dispersion, whereinthe synergistic pesticidal compositions may be dispersed in water orother agriculturally suitable liquid carrier.

In certain embodiments, the synergistic pesticidal compositions may bein the form of solution in an appropriate organic solvent. In oneembodiment, the spray oils, which are widely used in agriculturalchemistry, may be used as the organic solvent for the synergisticpesticidal compositions.

In one particular embodiment, the method of controlling pests comprisesapplying a pesticidal composition near a population of pests, whereinthe pesticidal composition comprises a synergistically effective amountof a chloride channel activator compound in combination with a pesticideselected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide(II), or any agriculturally acceptable salt thereof.

In some embodiments, the method of controlling pests comprises applyinga pesticidal composition near a population of pests, wherein thepesticidal composition comprises a synergistically effective amount ofan avermectins-based or a milbemycins-based compound in combination witha pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide(II) or any agriculturally acceptable salt thereof.

In other embodiments, the method of controlling pests comprises applyinga pesticidal composition near a population of pests, wherein thepesticidal composition comprises a synergistically effective amount ofthe pesticide in combination with at least one of abamectin, emamectinbenzoate, lepimectin, and milbemectin.

In further embodiments, the method of controlling pests comprisesapplying a pesticidal composition near a population of pests, whereinthe pesticidal composition comprises a synergistically effective amountof emamectin benzoate in combination with a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide (I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide (II) or any agriculturally acceptable salt thereof.

The control of pests may be achieved by applying a pesticidallyeffective amount of the synergistic pesticidal compositions in form ofsprays, topical treatment, gels, seed coatings, microcapsulations,systemic uptake, baits, eartags, boluses, foggers, fumigants aerosols,dusts, or the like.

These disclosed pesticidal compositions may be used, for example, asnematicides, acaricides, miticides, and/or molluscicides.

The pesticidal composition of the present disclosure may be used tocontrol a wide variety of insects. As a non-limiting example, in one ormore embodiments, the pesticidal composition may be used to control oneor more members of at least one of Phylum Arthropoda, Phylum Nematoda,Subphylum Chelicerata, Subphylum Myriapoda, Subphylum Hexapoda, ClassInsecta, Class Arachnida, and Class Symphyla. In at least someembodiments, the method of the present disclosure may be used to controlone or more members of at least one of Class Insecta and ClassArachnida.

As a non-limiting example, in one or more embodiments, the method of thepresent disclosure may be used to control one or more members of atleast one of Phylum Arthropoda, Phylum Nematoda, Subphylum Chelicerata,Subphylum Myriapoda, Subphylum Hexapoda, Class Insecta, Class Arachnida,and Class Symphyla. In at least some embodiments, the method of thepresent disclosure may be used to control one or more members of atleast one of Class Insecta and Class Arachnida.

In additional embodiments, the method of the present disclosure may beused to control members of the Order Coleoptera (beetles) including, butnot limited to, Acanthoscelides spp. (weevils), Acanthoscelides obtectus(common bean weevil), Agrilus planipennis (emerald ash borer), Agriotesspp. (wireworms), Anoplophora glabripennis (Asian longhorned beetle),Anthonomus spp. (weevils), Anthonomus grandis (boll weevil), Aphidiusspp., Apion spp. (weevils), Apogonia spp. (grubs), Ataenius spretulus(Black Turfgrass Ataenius), Atomaria linearis (pygmy mangold beetle),Aulacophore spp., Bothynoderes punctiventris (beet root weevil), Bruchusspp. (weevils), Bruchus pisorum (pea weevil), Cacoesia spp.,Callosobruchus maculatus (southern cow pea weevil), Carpophilushemipteras (dried fruit beetle), Cassida vittata, Cerosterna spp.,Cerotoma spp. (chrysomelids), Cerotoma trifurcata (bean leaf beetle),Ceutorhynchus spp. (weevils), Ceutorhynchus assimilis (cabbage seedpodweevil), Ceutorhynchus napi (cabbage curculio), Chaetocnema spp.(chrysomelids), Colaspis spp. (soil beetles), Conoderus scalaris,Conoderus stigmosus, Conotrachelus nenuphar (plum curculio), Cotinusnitidis (Green June beetle), Crioceris asparagi (asparagus beetle),Cryptolestes ferrugineus (rusty grain beetle), Cryptolestes pusillus(flat grain beetle), Cryptolestes turcicus (Turkish grain beetle),Ctenicera spp. (wireworms), Curculio spp. (weevils), Cyclocephala spp.(grubs), Cylindrocpturus adspersus (sunflower stem weevil), Deporausmarginatus (mango leaf-cutting weevil), Dermestes lardarius (larderbeetle), Dermestes maculates (hide beetle), Diabrotica spp.(chrysomelids), Epilachna varivestis (Mexican bean beetle), Faustinuscubae, Hylobius pales (pales weevil), Hypera spp. (weevils), Hyperapostica (alfalfa weevil), Hyperdoes spp. (Hyperodes weevil),Hypothenemus hampei (coffee berry beetle), Ips spp. (engravers),Lasioderma serricorne (cigarette beetle), Leptinotarsa decemlineata(Colorado potato beetle), Liogenys fuscus, Liogenys suturalis,Lissorhoptrus oryzophilus (rice water weevil), Lyctus spp. (woodbeetles/powder post beetles), Maecolaspis joliveti, Megascelis spp.,Melanotus communis, Meligethes spp., Meligethes aeneus (blossom beetle),Melolontha melolontha (common European cockchafer), Oberea brevis,Oberea linearis, Oryctes rhinoceros (date palm beetle), Oryzaephilusmercator (merchant grain beetle), Oryzaephilus suninamensis (sawtoothedgrain beetle), Otiorhynchus spp. (weevils), Oulema melanopus (cerealleaf beetle), Oulema oryzae, Pantomorus spp. (weevils), Phyllophaga spp.(May/June beetle), Phyllophaga cuyabana (chrysomelids), Phynchites spp.,Popillia japonica (Japanese beetle), Prostephanus truncates (largergrain borer), Rhizopertha dominica (lesser grain borer), Rhizotrogusspp. (European chafer), Rhynchophorus spp. (weevils), Scolytus spp.(wood beetles), Shenophorus spp. (Billbug), Sitona lineatus (pea leafweevil), Sitophilus spp. (grain weevils), Sitophilus granaries (granaryweevil), Sitophilus oryzae (rice weevil), Stegobium paniceum (drugstorebeetle), Tribolium spp. (flour beetles), Tribolium castaneum (red flourbeetle), Tribolium confusum (confused flour beetle), Trogodermavariabile (warehouse beetle), and Zabrus tenebioides.

In other embodiments, the method of the present disclosure may also beused to control members of the Order Dermaptera (earwigs).

In additional embodiments, the method of the present disclosure may beused to control members of the Order Dictyoptera (cockroaches)including, but is not limited to, Blattella germanica (Germancockroach), Blatta orientalis (oriental cockroach), Parcoblattapennylvanica, Periplaneta americana (American cockroach), Periplanetaaustraloasiae (Australian cockroach), Periplaneta brunnea (browncockroach), Periplaneta fuliginosa (smokybrown cockroach), Pyncoselussuninamensis (Surinam cockroach), and Supella longipalpa (brownbandedcockroach).

In further embodiments, the method of the present disclosure may be usedto control members of the Order Diptera (true flies) including, but isnot limited to, Aedes spp. (mosquitoes), Agromyza frontella (alfalfablotch leafminer), Agromyza spp. (leaf miner flies), Anastrepha spp.(fruit flies), Anastrepha suspensa (Caribbean fruit fly), Anopheles spp.(mosquitoes), Bactrocera spp. (fruit flies), Bactrocera cucurbitae(melon fly), Bactrocera dorsalis (oriental fruit fly), Ceratitis spp.(fruit flies), Ceratitis capitata (Mediterranean fruit fly), Chrysopsspp. (deer flies), Cochliomyia spp. (screwworms), Contarinia spp. (Gallmidges), Culex spp. (mosquitoes), Dasineura spp. (gall midges),Dasineura brassicae (cabbage gall midge), Delia spp., Delia platura(seedcorn maggot), Drosophila spp. (vinegar flies), Fannia spp. (filthflies), Fannia canicularis (little house fly), Fannia scalaris (latrinefly), Gasterophilus intestinalis (horse bot fly), Gracillia perseae,Haematobia irritans (horn fly), Hylemyia spp. (root maggots), Hypodermalineatum (common cattle grub), Liriomyza spp. (leafminer flies),Liriomyza brassica (serpentine leafminer), Liriomyza sativae (vegetableleafminer), Melophagus ovinus (sheep ked), Musca spp. (muscid flies),Musca autumnalis (face fly), Musca domestica (house fly), Oestrus ovis(sheep bot fly), Oscinella frit (frit fly), Pegomyia betae (beetleafminer), Phorbia spp., Psila rosae (carrot rust fly), Rhagoletiscerasi (cherry fruit fly), Rhagoletis pomonella (apple maggot),Sitodiplosis mosellana (orange wheat blossom midge), Stomoxys calcitrans(stable fly), Tabanus spp. (horse flies), and Tipula spp. (crane flies).

In other embodiments, the method of the present disclosure may be usedto control members of the Order Hemiptera Sub-order Heteroptera (truebugs) including, but is not limited to, Acrosternum hilare (green stinkbug), Blissus leucopterus (chinch bug), Bragada hilaris, Calocorisnorvegicus (potato mirid), Cimex hemipterus (tropical bed bug), Cimexlectularius (bed bug), Dagbertus fasciatus, Dichelops furcatus,Dysdercus suturellus (cotton stainer), Edessa meditabunda, Eurygastermaura (cereal bug), Euschistus heros, Euschistus servus (brown stinkbug), Helopeltis antonii, Helopeltis theivora (tea blight plantbug),Lagynotomus spp. (stink bugs), Leptocorisa oratorius, Leptocorisavaricornis, Lygus spp. (plant bugs), Lygus hesperus (western tarnishedplant bug), Lygus lineolaris (tarnished plant bug), Maconellicoccushirsutus, Neurocolpus longirostris, Nezara viridula (southern greenstink bug), Phytocoris spp. (plant bugs), Phytocoris californicus,Phytocoris relativus, Piezodorus guildinii (redbanded stink bug),Poecilocapsus lineatus (fourlined plant bug), Psallus vaccinicola,Pseudacysta perseae, Scaptocoris castanea, and Triatoma spp.(bloodsucking conenose bugs/kissing bugs).

In additional embodiments, the method of the present disclosure may beused to control members of the Order Hemiptera, Sub-ordersAuchenorrhyncha (Free-living Hemipterans) and Sternorrhyncha(Plant-parasitic Hemipterans) (aphids, scales, whiteflies, leaflhoppers)including, but is not limited to, Acrythosiphon pisum (pea aphid),Adelges spp. (adelgids), Aleurodes proletella (cabbage whitefly),Aleurodicus disperses, Aleurothrixus floccosus (woolly whitefly),Aluacaspis spp., Amrasca bigutella bigutella, Aphrophora spp.(leafhoppers), Aonidiella aurantii (California red scale), Aphis spp.(aphids), Aphis gossypii (cotton aphid), Aphis pomi (apple aphid),Aulacorthum solani (foxglove aphid), Bemisia spp. (whiteflies), Bemisiaargentifolii, Bemisia tabaci (sweetpotato whitefly), Brachycolus noxius(Russian aphid), Brachycorynella asparagi (asparagus aphid), Brevenniarehi, Brevicoryne brassicae (cabbage aphid), Ceroplastes spp. (scales),Ceroplastes rubens (red wax scale), Chionaspis spp. (scales),Chrysomphalus spp. (scales), Chrysomphalus aonidum (Florida red scale)Coccus spp. (scales), Coccus pseudomagnoliarum (citricola scale),Dysaphis plantaginea (rosy apple aphid), Empoasca spp. (leafhoppers),Eriosoma lanigerum (woolly apple aphid), Icerya purchasi (cottonycushion scale), Idioscopus nitidulus (mango leafhopper), Laodelphaxstriatellus (smaller brown planthopper), Lepidosaphes spp., Macrosiphumspp., Macrosiphum euphorbiae (potato aphid), Macrosiphum granarium(English grain aphid), Macrosiphum rosae (rose aphid), Macrostelesquadrilineatus (aster leafhopper), Mahanarva frimbiolata, Metopolophiumdirhodum (rose grain aphid), Mictis longicornis, Myzus spp., Myzuspersicae (green peach aphid), Nephotettix spp. (leafhoppers),Nephotettix cinctipes (green leafhopper), Nilaparvata lugens (brownplanthopper), Paratrioza cockerelli (tomato psyllid), Parlatoriapergandii (chaff scale), Parlatoria ziziphi (ebony scale), Peregrinusmaidis (corn delphacid), Philaenus spp. (spittlebugs), Phylloxeravitifoliae (grape phylloxera), Physokermes piceae (spruce bud scale),Planococcus spp. (mealybugs), Planococcus citri (citrus mealybug),Planococcus ficus (grape mealybug), Pseudococcus spp. (mealybugs),Pseudococcus brevipes (pine apple mealybug), Quadraspidiotus perniciosus(San Jose scale), Rhopalosiphum spp. (aphids), Rhopalosiphum maidis(corn leaf aphid), Rhopalosiphum padi (oat bird-cherry aphid), Saissetiaspp. (scales), Saissetia oleae (black scale), Schizaphis graminum(greenbug), Sitobion avenae (English grain aphid), Sogatella furcifera(white-backed planthopper), Therioaphis spp. (aphids), Toumeyella spp.(scales), Toxoptera spp. (aphids), Trialeurodes spp. (whiteflies),Trialeurodes vaporariorum (greenhouse whitefly), Trialeurodesabutiloneus (bandedwing whitefly), Unaspis spp. (scales), Unaspisyanonensis (arrowhead scale), and Zulia entreriana. In at least someembodiments, the method of the present disclosure may be used to controlMyzus persicae.

In other embodiments, the method of the present disclosure may be usedto control members of the Order Hymenoptera (ants, wasps, and sawflies)including, but not limited to, Acromyrrmex spp., Athalia rosae, Attaspp. (leafcutting ants), Camponotus spp. (carpenter ants), Diprion spp.(sawflies), Formica spp. (ants), Iridomyrmex humilis (Argentine ant),Monomorium spp., Monomorium minumum (little black ant), Monomoriumpharaonis (Pharaoh ant), Neodiprion spp. (sawflies), Pogonomyrmex spp.(harvester ants), Polistes spp. (paper wasps), Solenopsis spp. (fireants), Tapoinoma sessile (odorous house ant), Tetranomorium spp.(pavement ants), Vespula spp. (yellow jackets), and Xylocopa spp.(carpenter bees).

In certain embodiments, the method of the present disclosure may be usedto control members of the Order Isoptera (termites) including, but notlimited to, Coptotermes spp., Coptotermes curvignathus, Coptotermesfrenchii, Coptotermes formosanus (Formosan subterranean termite),Cornitermes spp. (nasute termites), Cryptotermes spp. (drywoodtermites), Heterotermes spp. (desert subterranean termites),Heterotermes aureus, Kalotermes spp. (drywood termites), Incistitermesspp. (drywood termites), Macrotermes spp. (fungus growing termites),Marginitermes spp. (drywood termites), Microcerotermes spp. (harvestertermites), Microtermes obesi, Procornitermes spp., Reticulitermes spp.(subterranean termites), Reticulitermes banyulensis, Reticulitermesgrassei, Reticulitermes flavipes (eastern subterranean termite),Reticulitermes hageni, Reticulitermes hesperus (western subterraneantermite), Reticulitermes santonensis, Reticulitermes speratus,Reticulitermes tibialis, Reticulitermes virginicus, Schedorhinotermesspp., and Zootermopsis spp. (rotten-wood termites).

In additional embodiments, the method of the present disclosure may beused to control members of the Order Lepidoptera (moths and butterflies)including, but not limited to, Achoea janata, Adoxophyes spp.,Adoxophyes orana, Agrotis spp. (cutworms), Agrotis ipsilon (blackcutworm), Alabama argillacea (cotton leafworm), Amorbia cuneana,Amyelosis transitella (navel orangeworm), Anacamptodes defectaria,Anarsia lineatella (peach twig borer), Anomis sabulifera (jute looper),Anticarsia gemmatalis (velvetbean caterpillar), Archips argyrospila(fruittree leafroller), Archips rosana (rose leaf roller), Argyrotaeniaspp. (tortricid moths), Argyrotaenia citrana (orange tortrix),Autographa gamma, Bonagota cranaodes, Borbo cinnara (rice leaf folder),Bucculatrix thurberiella (cotton leafperforator), Caloptilia spp. (leafminers), Capua reticulana, Carposina niponensis (peach fruit moth),Chilo spp., Chlumetia transversa (mango shoot borer), Choristoneurarosaceana (obliquebanded leafroller), Chrysodeixis spp., Cnaphalocerusmedinalis (grass leafroller), Colias spp., Conpomorpha cramerella,Cossus cossus (carpenter moth), Crambus spp. (Sod webworms),Cydiafunebrana (plum fruit moth), Cydia molesta (oriental fruit moth),Cydia nignicana (pea moth), Cydia pomonella (codling moth), Darnadiducta, Diaphania spp. (stem borers), Diatraea spp. (stalk borers),Diatraea saccharalis (sugarcane borer), Diatraea graniosella(southwester corn borer), Earias spp. (bollworms), Earias insulata(Egyptian bollworm), Earias vitella (rough northern bollworm),Ecdytopopha aurantianum, Elasmopalpus lignosellus (lesser cornstalkborer), Epiphysias postruttana (light brown apple moth), Ephestia spp.(flour moths), Ephestia cautella (almond moth), Ephestia elutella(tobbaco moth), Ephestia kuehniella (Mediterranean flour moth), Epimecesspp., Epinotia aporema, Erionota thrax (banana skipper), Eupoeciliaambiguella (grape berry moth), Euxoa auxiliaris (army cutworm), Feltiaspp. (cutworms), Gortyna spp. (stemborers), Grapholita molesta (orientalfruit moth), Hedylepta indicata (bean leaf webber), Helicoverpa spp.(noctuid moths), Helicoverpa armigera (cotton bollworm), Helicoverpa zea(bollworm/corn earworm), Heliothis spp. (noctuid moths), Heliothisvirescens (tobacco budworm), Hellula undalis (cabbage webworm),Indarbela spp. (root borers), Keiferia lycopersicella (tomato pinworm),Leucinodes orbonalis (eggplant fruit borer), Leucoptera malifoliella,Lithocollectis spp., Lobesia botrana (grape fruit moth), Loxagrotis spp.(noctuid moths), Loxagrotis albicosta (western bean cutworm), Lymantriadispar (gypsy moth), Lyonetia clerkella (apple leaf miner), Mahasenacorbetti (oil palm bagworm), Malacosoma spp. (tent caterpillars),Mamestra brassicae (cabbage armyworm), Maruca testulalis (bean podborer), Metisa plana (bagworm), Mythimna unipuncta (true armyworm),Neoleucinodes elegantalis (small tomato borer), Nymphula depunctalis(rice caseworm), Operophthera brumata (winter moth), Ostrinia nubilalis(European corn borer), Oxydia vesulia, Pandemis cerasana (common curranttortrix), Pandemis heparana (brown apple tortrix), Papilio demodocus,Pectinophora gossypiella (pink bollworm), Peridroma spp. (cutworms),Peridroma saucia (variegated cutworm), Perileucoptera coffeella (whitecoffee leafminer), Phthorimaea operculella (potato tuber moth),Phyllocnisitis citrella, Phyllonorycter spp. (leafminers), Pieris rapae(imported cabbageworm), Plathypena scabra, Plodia interpunctella (Indianmeal moth), Plutella xylostella (diamondback moth), Polychrosis viteana(grape berry moth), Prays endocarps, Prays oleae (olive moth),Pseudaletia spp. (noctuid moths), Pseudaletia unipunctata (armyworm),Pseudoplusia includens (soybean looper), Rachiplusia nu, Scirpophagaincertulas, Sesamia spp. (stemborers), Sesamia inferens (pink rice stemborer), Sesamia nonagrioides, Setora nitens, Sitotroga cerealella(Angoumois grain moth), Sparganothis pilleriana, Spodoptera spp.(armyworms), Spodoptera exigua (beet armyworm), Spodoptera fugiperda(fall armyworm), Spodoptera oridania (southern armyworm), Synanthedonspp. (root borers), Thecla basilides, Thermisia gemmatalis, Tineolabisselliella (webbing clothes moth), Trichoplusia ni (cabbage looper),Tuta absoluta, Yponomeuta spp., Zeuzera coffeae (red branch borer), andZeuzera pyrina (leopard moth). In at least some embodiments, the methodof the present disclosure may be used to control Spodoptera exigua.

The method of the present disclosure may be used to also control membersof the Order Mallophaga (chewing lice) including, but not limited to,Bovicola ovis (sheep biting louse), Menacanthus stramineus (chicken bodylouse), and Menopon gallinea (common hen louse).

In additional embodiments, the method of the present disclosure may beused to control members of the Order Orthoptera (grasshoppers, locusts,and crickets) including, but not limited to, Anabrus simplex (Mormoncricket), Gryllotalpidae (mole crickets), Locusta migratoria, Melanoplusspp. (grasshoppers), Microcentrum retinerve (angularwinged katydid),Pterophylla spp. (kaydids), chistocerca gregaria, Scudderia furcata(forktailed bush katydid), and Valanga nigricorni.

In other embodiments, the method of the present disclosure may be usedto control members of the Order Phthiraptera (sucking lice) including,but not limited to, Haematopinus spp. (cattle and hog lice), Linognathusovillus (sheep louse), Pediculus humanus capitis (human body louse),Pediculus humanus humanus (human body lice), and Pthirus pubis (crablouse).

In particular embodiments, the method of the present disclosure may beused to control members of the Order Siphonaptera (fleas) including, butnot limited to, Ctenocephalides canis (dog flea), Ctenocephalides felis(cat flea), and Pulex irritans (human flea).

In additional embodiments, the method of the present disclosure may beused to control members of the Order Thysanoptera (thrips) including,but not limited to, Caliothrips fasciatus (bean thrips), Caliothripsphaseoli, Frankliniella fusca (tobacco thrips), Frankliniellaoccidentalis (western flower thrips), Frankliniella shultzei,Frankliniella williamsi (corn thrips), Heliothrips haemorrhaidalis(greenhouse thrips), Riphiphorothrips cruentatus, Scirtothrips spp.,Scirtothrips citri (citrus thrips), Scirtothrips dorsalis (yellow teathrips), Taeniothrips rhopalantennalis, Thrips spp., Thrips tabaci(onion thrips), and Thrips hawaiiensis (Hawaiian flower thrips).

The method of the present disclosure may be used to also control membersof the Order Thysanura (bristletails) including, but not limited to,Lepisma spp. (silverfish) and Thermobia spp. (firebrats).

In further embodiments, the method of the present disclosure may be usedto control members of the Order Acari (mites and ticks) including, butnot limited to, Acarapsis woodi (tracheal mite of honeybees), Acarusspp. (food mites), Acarus siro (grain mite), Aceria mangiferae (mangobud mite), Aculops spp., Aculops lycopersici (tomato russet mite),Aculops pelekasi, Aculus pelekassi, Aculus schlechtendali (apple rustmite), Amblyomma americanum (lone star tick), Boophilus spp. (ticks),Brevipalpus obovatus (privet mite), Brevipalpus phoenicis (red and blackflat mite), Demodex spp. (mange mites), Dermacentor spp. (hard ticks),Dermacentor variabilis (american dog tick), Dermatophagoidespteronyssinus (house dust mite), Eotetranycus spp., Eotetranychuscarpini (yellow spider mite), Epitimerus spp., Eriophyes spp., Ixodesspp. (ticks), Metatetranycus spp., Notoedres cati, Oligonychus spp.,Oligonychus coffee, Oligonychus ilicus (southern red mite), Panonychusspp., Panonychus citri (citrus red mite), Panonychus ulmi (European redmite), Phyllocoptruta oleivora (citrus rust mite), Polyphagotarsonemunlatus (broad mite), Rhipicephalus sanguineus (brown dog tick),Rhizoglyphus spp. (bulb mites), Sarcoptes scabiei (itch mite),Tegolophus perseaflorae, Tetranychus spp., Tetranychus urticae(twospotted spider mite), and Varroa destructor (honey bee mite).

In additional embodiments, the method of the present disclosure may beused to control members of the Order Nematoda (nematodes) including, butnot limited to, Aphelenchoides spp. (foliar nematodes), Belonolaimusspp. (sting nematodes), Criconemella spp. (ring nematodes), Dirofilariaimmitis (dog heartworm), Ditylenchus spp. (stem and bulb nematodes),Heterodera spp. (cyst nematodes), Heterodera zeae (corn cyst nematode),Hirschmanniella spp. (root nematodes), Hoplolaimus spp. (lancenematodes), Meloidogyne spp. (root knot nematodes), Meloidogyneincognita (root knot nematode), Onchocerca volvulus (hook-tail worm),Pratylenchus spp. (lesion nematodes), Radopholus spp. (burrowingnematodes), and Rotylenchus reniformis (kidney-shaped nematode).

In at least some embodiments, the method of the present disclosure maybe used to control at least one insect in one or more of the OrdersLepidoptera, Coleoptera, Hemiptera, Thysanoptera, Isoptera, Orthoptera,Diptera, Hymenoptera, and Siphonaptera, and at least one mite in theOrder Acari.

In some embodiments, the method of controlling an insect may compriseapplying a pesticidal composition near a population of pests, whereinthe pesticidal composition comprises a synergistically effective amountof a chloride channel activator compound in combination with a pesticideselected from N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide(II) or any agriculturally acceptable salt thereof, and wherein thepests comprise sap feeding insects, chewing insects, or both.

In other embodiments, the method of controlling an insect may compriseapplying a pesticidal composition near a population of pests, whereinthe pesticidal composition comprises a synergistically effective amountof a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide(II) or any agriculturally acceptable salt thereof, and at least one ofabamectin, emamectin benzoate, lepimectin, and milbemectin, wherein thepests comprise sap feeding insects, chewing insects, or both.

In further embodiments, the method of controlling an insect may compriseapplying a pesticidal composition near a population of pests, whereinthe pesticidal composition comprises a synergistically effective amountof an avermectins-based or a milbemycins-based compound in combinationwith a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide(II) or any agriculturally acceptable salt thereof, wherein the pestscomprise at least one of diamondback moth, Plutella xylostella; SouthAmerican brown stink bug, Euschistus heros; and Western plant bug, LygusHesperus.

In yet further embodiments, the method of controlling an insect maycomprise applying a pesticidal composition near a population of pests,wherein the pesticidal composition comprises a synergistically effectiveamount of emamectin benzoate and a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide (II), or any agriculturally acceptable salt thereof, andwherein the pests comprise at least one of diamondback moth, Plutellaxylostella; South American brown stink bug, Euschistus heros; andWestern plant bug, Lygus Hesperus.

In one embodiment of present disclosure, the pesticidal composition maybe used in conjunction (such as, in a compositional mixture, or asimultaneous or sequential application) with one or more compoundshaving acaricidal, algicidal, avicidal, bactericidal, fungicidal,herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal,and/or virucidal properties.

In another embodiment of present disclosure, the pesticidal compositionmay be used in conjunction (such as, in a compositional mixture, or asimultaneous or sequential application) with one or more compounds thatare antifeedants, bird repellents, chemosterilants, herbicide safeners,insect attractants, insect repellents, mammal repellents, matingdisrupters, plant activators, plant growth regulators, and/orsynergists.

The pesticidal compositions of present disclosure show a synergisticeffect, providing superior pest control at lower pesticidally effectiveamounts of the combined active compounds than when a chloride channelactivator compound or a pesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide (I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide (II), or any agriculturally acceptable salt thereof is usedalone.

The pesticidal compositions of present disclosure may have highsynergistic pest control and allow for a lower effective dosage rate, anincreased environmental safety, and a reduced incidence of pestresistance.

The following examples serve to explain embodiments of the presentinvention in more detail. These examples should not be construed asbeing exhaustive or exclusive as to the scope of this disclosure.

EXAMPLES Example 1 Preparation of3-((3,3,3-trifluoropropyl)thio)propanoyl chloride

A dry five-liter round bottom flask equipped with magnetic stirrer,nitrogen inlet, reflux condenser, and thermometer, was charged with3-((3,3,3-trifluoropropyl)thio)propanoic acid (prepared as described inthe PCT Publication No. WO 2013/062981 to Niyaz et al.) (188 g, 883mmol) in dichloromethane (CH₂Cl₂) (3 L). Thionyl chloride (525 g, 321mL, 4.42 mol) was added dropwise over 50 minutes. The reaction mixturewas heated to reflux (about 36° C.) for two hours, then cooled to roomtemperature (about 22° C.). The resulting mixture was concentrated undervacuum on a rotary evaporator, followed by distillation (40 Torr,product collected at a temperature of from about 123° C. to about 127°C.) to provide the title compound as a clear colorless liquid (177.3 g,86%): ¹H NMR (400 MHz, CDCl₃) δ 3.20 (t, J=7.1 Hz, 2H), 2.86 (t, J=7.1Hz, 2H), 2.78-2.67 (m, 2H), 2.48-2.31 (m, 2H); ¹⁹F NMR (376 MHz, CDCl₃)δ −66.42, −66.43, −66.44, −66.44.

Example 2 Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine(prepared as described in the U.S. Publication No. 2012/0110702 to Yapet al.) (10 g, 44.9 mmol) in CH₂Cl₂ (100 mL) at a temperature of about0° C. and under N₂ was added pyridine (5.45 mL, 67.4 mmol),4-dimethylaminopyridine (DMAP) (2.74 g, 22.45 mmol), and3-((3,3,3-trifluoropropyl)thio) propanoyl chloride (9.91 g, 44.9 mmol),sequentially. The reaction was warmed to room temperature and stirredfor one hour. The reaction mixture was poured into water (100 mL), andthe resulting mixture was stirred for five minutes. The mixture wastransferred to a separatory funnel, and the layers were separated. Theaqueous phase was extracted with CH₂Cl₂ (3×50 mL), and the combinedorganic extracts were dried over sodium sulfate (Na₂SO₄), filtered, andconcentrated in vacuo. The crude product was purified via normal phaseflash chromatography (0% to 100% EtOAc/CH₂Cl₂) to provide the desiredproduct as a pale yellow solid (17.21 g, 89%): IR (thin film) 1659 cm⁻¹;¹H NMR (400 MHz, CDCl₃) δ 8.95 (d, J=2.6 Hz, 1H), 8.63 (dd, J=4.7, 1.3Hz, 1H), 8.05 (ddd, J=8.3, 2.7, 1.4 Hz, 1H), 7.96 (s, 1H), 7.47 (dd,J=8.3, 4.8 Hz, 1H), 3.72 (q, J=7.1 Hz, 2H), 2.84 (t, J=7.2 Hz, 2H), 2.66(m, 2H), 237 (t, J=7.2 Hz, 2H), 2.44 (m, 2H), 1.17 (t, J=7.2 Hz, 3H);ESIMS m/z 409 ([M+2H]⁺).

Example 3 Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide(II)

To a solution ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I) (500 mg, 1.229 mmol) in hexafluoroisopropanol (5 mL) stirring atroom temperature was added 30% hydrogen peroxide (523 mg, 4.92 mmol).The solution was stirred at room temperature for 15 minutes. It wasquenched with saturated sodium sulfite solution and extracted withCH₂Cl₂. Silica gel chromatography (0%-10% MeOH/CH₂Cl₂) gave the titlecompound as white semi-solid (495 mg, 95%): IR (thin film) 1660 cm⁻¹; ¹HNMR (400 MHz, CDCl₃) δ 8.96 (d, J=2.4 Hz, 1H), 8.64 (dd, J=4.7, 1.4 Hz,1H), 8.07-8.00 (m, 2H), 7.46 (ddd, J=8.3, 4.8, 0.7 Hz, 1H), 3.85-3.61(m, 2H), 3.23-3.08 (m, 1H), 3.03-2.76 (m, 3H), 2.74-2.52 (m, 4H), 1.18(t, J=7.2 Hz, 3H); ESIMS m/z 423 ([M+H]⁺).

Example 4 Determination of the Existence of Synergic Effect

The method described in Colby S. R., “Calculating Synergistic andAntagonistic Responses of Herbicide Combinations,” Weeds, 1967, 15,20-22 was used to determine an existence of synergic effect between thechloride channel activator compound and the pesticide (I), (II), or anyagriculturally acceptable salt thereof in the formulated pesticidalcomposition. In this method, the percent insect control of theformulated pesticidal composition as observed in the study was comparedto the “expected” percent control (E) as calculated by equation (1)(hereinafter “Colby's equation”) below:

$\begin{matrix}{E = {X + Y - \left( \frac{XY}{100} \right)}} & (1)\end{matrix}$

where

X is the percentage of control with the first pesticide at a given rate(p),

Y is the percentage of control with the second pesticide at a given rate(q), and

E is the expected control by the first and second pesticide at a rate ofp+q.

If the observed percent control of the formulated pesticidal is greaterthan E, there is a synergistic effect between the chloride channelactivator compound and the pesticide (I), (II), or any agriculturallyacceptable salt thereof in the formulated pesticidal composition. If theobserved percent control of the formulated pesticidal is equaled to orless than E, there is no synergistic effect between the chloride channelactivator compound and the pesticide (I), (II), or any agriculturallyacceptable salt thereof in the formulated pesticidal composition.

Example 5 Synergistic Effect ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I) and Emamectin Benzoate Against Diamondback Moth, Plutella xylostellaExample 5A

A pesticidal composition was prepared by thoroughly mixing about 0.0025weight % ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide (hereinafter “compound I”) with about 0.000078 weight % ofemamectin benzoate.

Bioassays were performed for different active compounds. Cabbage plantswith about two to three new-growth—true leaf stage were treated withdifferent active compounds using a track sprayer application at 400 L/Haspray volume. Three second instar diamondback moth, Plutella xylostella,were infested onto each leaf disc. The percent control determined threedays after the treatment were as shown in table 2. The percent controlof the pesticidal composition against diamondback moth, Plutellaxylostella, was determined as the “Observed” action, and compared tothose obtained by using about 0.0025 weight % of compound II, and usingabout 0.000078 weight % of emamectin benzoate alone. The “Colby'sExpected Action” was calculated using Colby's equation as discussedpreviously.

As shown in table 2, the observed percent control of the pesticidalcomposition against diamondback moth (100%) was higher than the expectedpercentage control according to Colby's equation (91.7%). This was 9%improvement over the Colby's expected action. Therefore, the pesticidalcomposition comprising 0.0025 weight % of compound I and about 0.000078weight % of emamectin benzoate showed synergistic effect againstdiamondback moth.

TABLE 2 % Control Treatment for Dose Rate Three Days Diamondback Moth(weight %) After Treatment Compound I 0.0025  4.35% Emamectin Benzoate0.000078 91.3% Compound I (+) Emamectin 0.0025 + 0.000078  100% BenzoateObserved Action Compound I (+) Emamectin 0.0025 + 0.000078 91.7%Benzoate Colby's Expected Action Compound I (+) Emamectin 0.0025 +0.000078  8.3% Benzoate Differences: Observed vs. Expected

Example 5B

A pesticidal composition was prepared by thoroughly mixing about 0.0025weight % of compound I with about 0.000039 weight % of emamectinbenzoate.

Bioassays were performed wherein different active compounds were testedagainst diamondback moth, Plutella xylostella, using the proceduredescribed in example 5A. The percent control against diamondback mothdetermined three days after the treatment were as shown in table 3.

TABLE 3 % Control Treatment for Dose Rate Three Days Diamondback Moth(weight %) After Treatment Compound I 0.0025   4.35% Emamectin Benzoate0.000039 73.91% Compound I (+) Emamectin 0.0025 + 0.000039 95.65%Benzoate Observed Action Compound I (+) Emamectin 0.0025 + 0.00003975.00% Benzoate Colby's Expected Action Compound I (+) Emamectin0.0025 + 0.000039 20.65% Benzoate Differences: Observed vs. Expected

As shown in table 3, the observed percent control of the pesticidalcomposition against diamondback moth (95.65%) was higher than theexpected percentage control according to Colby's equation (75%). Thiswas about 27.5% improvement over the Colby's expected action. Therefore,the pesticidal composition comprising 0.0025 weight % of compound I andabout 0.000039 weight % of emamectin benzoate showed synergistic effectagainst diamondback moth.

Example 5C

A pesticidal composition was prepared by thoroughly mixing about0.000625 weight % of compound I with about 0.000039 weight % ofemamectin benzoate.

Bioassays were performed wherein different active compounds were testedagainst diamondback moth, Plutella xylostella, using the proceduredescribed in example 5A. The percent control against diamondback mothdetermined three days after the treatment were as shown in table 4.

TABLE 4 % Control Treatment for Dose Rate Three Days Diamondback Moth(weight %) After Treatment Compound I 0.000625    0% Emamectin Benzoate0.000039 73.91% Compound I (+) Emamectin 0.000625 + 0.000039 82.61%Benzoate Observed Action Compound I (+) Emamectin 0.000625 + 0.00003973.90% Benzoate Colby's Expected Action Compound I (+) Emamectin0.000625 + 0.000039  8.71% Benzoate Differences: Observed vs. Expected

As shown in table 4, compound I at a dose rate of 0.000625 weight %showed no control against diamondback moth three days after thetreatment. Furthermore, the observed percent control of the pesticidalcomposition against diamondback moth (82.61%) three days after thetreatment was higher than the expected percentage control according toColby's equation (73.90%). This was about 12% improvement over theColby's expected action. Therefore, the pesticidal compositioncomprising 0.000625 weight % of compound I and about 0.000039 weight %of emamectin benzoate showed synergistic effect against diamondbackmoth.

Example 6 Synergistic Effect ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I) and Emamectin Benzoate Against South American Brown Stink Bug,Euschistus heros

A pesticidal composition was prepared by thoroughly mixing about 0.04weight % of compound I with about 0.000156 weight % of emamectinbenzoate.

The active compounds were formulated in a 10% acetone solution with0.025% non-ionic surfactant, TWEEN® 20. Bioassays were performed foreach different active solution. Bean pieces (about one inch-long) wereused for the tests. Four bean pieces were placed in each tested activesolution and left there for 10 minutes. Bean pieces were taken out ofthe active solution, and each piece was placed in a well in a 32-welltray and allowed to air dry. Three third-instar nymphs of South Americanbrown stink bug, Euschistus heros, were infested into each well. Thepercent control determined after four days of the treatment were asshown in table 5.

TABLE 5 % Control Treatment for Dose Rate Four Days Brown Stink Bug(weight %) After Treatment Compound I 0.04    8% Emamectin Benzoate0.000156 25% Compound I (+) Emamectin 0.04 + 0.000156 42% BenzoateObserved Action Compound I (+) Emamectin 0.04 + 0.000156 31% BenzoateColby's Expected Action Compound I (+) Emamectin 0.04 + 0.000156 11%Benzoate Differences: Observed vs. Expected

The percent control of the pesticidal composition against South Americanbrown stink bug, Euschistus heros, was determined as the “Observed”action, and compared to those obtained by using about 0.04 weight % ofcompound I, and using about 0.000156 weight % of emamectin benzoatealone. The “Colby's Expected Action” was calculated using Colby'sequation as discussed previously.

As shown in table 5, the observed percent control of the pesticidalcomposition against brown stink bug (42%) was higher than the expectedpercentage control according to Colby's equation (31%). This was 35%improvement over the Colby's expected action. Therefore, the pesticidalcomposition comprising 0.04 weight % of compound I and about 0.000156weight % of emamectin benzoate showed synergistic effect against SouthAmerican brown stink bug, Euschistus heros.

Example 7 Synergistic Effect ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I) and Emamectin Benzoate Against Western Plant Bug, Lygus hesperus

A pesticidal composition was prepared by thoroughly mixing about 0.04weight % of compound I with about 0.20 weight % of emamectin benzoate.

The active compounds were formulated in a 10% acetone solution with0.025% non-ionic surfactant, TWEEN® 20. Bioassays were performed foreach different active solution. Bean pieces (about one inch-long) wereused for the tests. Four bean pieces were placed in each tested activesolution and left there for 10 minutes. Bean pieces were taken out ofthe active solution, and each piece was placed in a well in a 32-welltray and allowed to air dry. Three third-instar nymphs of Western plantbug, Lygus hesperus, were infested into each well. The percent controldetermined three days after the treatment were as shown in table 6. Thepercent control of the pesticidal composition against Lygus hesperus bugwas determined as the “Observed” action, and compared to those obtainedby using about 0.04 weight % of compound I, and using about 0.20 weight% of emamectin benzoate alone. The “Colby's Expected Action” wascalculated using Colby's equation as discussed previously.

As shown in table 6, the observed percent control of the pesticidalcomposition against Lygus hesperus bug was about 17% three days aftertreatment. On the other hand, compound I and emamectin benzoate, whenused alone, showed no control against Lygus hesperus bug three daysafter the treatment, and therefore the expected percentage controlaccording to Colby's equation was zero. Thus, the pesticidal compositioncomprising 0.04 weight % of compound I and 0.20 weight % of emamectinbenzoate showed synergistic effect against Western plant bug, Lygushesperus.

TABLE 6 % Control Treatment for Dose Rate Three Days Lygus hesperus(weight %) After Treatment Compound I 0.04 0% Emamectin Benzoate 0.20 0%Compound I (+) Emamectin 0.04 + 0.20 17%  Benzoate Observed ActionCompound I (+) Emamectin 0.04 + 0.20 0% Benzoate Colby's Expected ActionCompound I (+)Emamectin 0.04 + 0.20 17%  Benzoate Differences: Observedvs. Expected

Example 8 Synergistic Effect ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide(I) orN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide(II) and Emamectin Benzoate

A pesticidal composition may be prepared by thoroughly mixing compound I(weight %) or compound II (weight %) with emamectin benzoate (weight %).

The bioassays may be performed for different active compounds againstDiamondback Moth, Plutella xylostella, using the same procedure as thatdescribed in example 5. The percent control may be determined some timeafter the treatment.

The bioassays may be performed for different active compounds againstSouth American Brown Stink Bug, Euschistus heros, using the sameprocedure as that described for example 6. The percent control may bedetermined some time after the treatment.

The bioassays may be performed for different active compounds againstWestern Plant Bug, Lygus hesperus, using the same procedure as thatdescribed for example 7. The percent control may be determined some timeafter the treatment.

The observed percent control of the pesticidal composition againstDiamondback Moth, Plutella xylostella is expected to be higher than theexpected percentage control according to Colby's equation. Therefore,the pesticidal composition comprising compound I (weight %) or compoundII (weight %) and emamectin benzoate (weight %) is expected to showsynergistic effect against Diamondback Moth, Plutella xylostella.

The observed percent control of the pesticidal composition against SouthAmerican Brown Stink Bug, Euschistus heros is expected to be higher thanthe expected percentage control according to Colby's equation.Therefore, the pesticidal composition comprising compound I (weight %)or compound II (weight %) and emamectin benzoate (weight %) is expectedto show synergistic effect against South American Brown Stink Bug,Euschistus heros.

The observed percent control of the pesticidal composition againstWestern Plant Bug, Lygus hesperus is expected to be higher than theexpected percentage control according to Colby's equation. Therefore,the pesticidal composition comprising compound I (weight %) or compoundII (weight %) and emamectin benzoate (weight %) is expected to showsynergistic effect against Western Plant Bug, Lygus hesperus.

While the present disclosure may be susceptible to various modificationsand alternative forms, specific embodiments have been described by wayof example in detail herein. However, it should be understood that thepresent disclosure is not intended to be limited to the particular formsdisclosed. Rather, the present disclosure is to cover all modifications,equivalents, and alternatives falling within the scope of the presentdisclosure as defined by the following appended claims and their legalequivalents.

We claim:
 1. A pesticidal composition comprising a synergisticallyeffective amount of: a chloride channel activator compound; and apesticide selected fromN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-rifluoropropyl)thio)propanamide(I),N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3-trifluoropropyl)sulfinyl)propanamide(II), or any agriculturally acceptable salt thereof.


2. The composition of claim 1, wherein the chloride channel activatorcompound comprises an avermectins-based compound.
 3. The composition ofclaim 1, wherein the chloride channel activator compound comprises amilbemycins-based compound.
 4. The composition of claim 1, wherein thechloride channel activator compound comprises at least one of abamectin,emamectin benzoate, lepimectin, and milbemectin.
 5. The composition ofclaim 1, wherein the chloride channel activator compound comprisesemamectin benzoate.
 6. The composition of claim 1, further comprising aphytologically-acceptable inert carrier.
 7. The composition of claim 1,further comprising an additive selected from a surfactant, a stabilizer,an emetic agent, a disintegrating agent, an antifoaming agent, a wettingagent, a dispersing agent, a binding agent, dye, filler, or combinationsthereof.
 8. The composition of claim 1, further comprising one or morecompounds having acaricidal, algicidal, avicidal, bactericidal,fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal,rodenticidal, virucidal or combinations thereof properties.
 9. Thecomposition of claim 1, further comprising one or more compounds thatare antifeedants, bird repellents, chemosterilants, herbicide safeners,insect attractants, insect repellents, mammal repellents, matingdisrupters, plant activators, plant growth regulators, synergists, orcombinations thereof.
 10. The composition of claim 1, wherein a weightratio of the pesticide selected from (I), (II) or any agriculturallyacceptable salt thereof to the chloride channel activator compound is nomore than about 2048:1.
 11. The composition of claim 1, wherein a weightratio of the pesticide selected from (I), (II) or any agriculturallyacceptable salt thereof to the chloride channel activator compound is nomore than about 256:1.
 12. The composition of claim 1, wherein a weightratio of the pesticide selected from (I), (II) or any agriculturallyacceptable salt thereof to the chloride channel activator compound is nomore than about 64:1.
 13. The composition of claim 1, wherein a weightratio of the pesticide selected from (I), (II) or any agriculturallyacceptable salt thereof to the chloride channel activator compound is nomore than about 32:1.
 14. The composition of claim 1, wherein a weightratio of the pesticide selected from (I), (II) or any agriculturallyacceptable salt thereof to the chloride channel activator compound is nomore than about 16:1
 15. The composition of claim 1, wherein the weightratio of the pesticide (I), (II), or any agriculturally acceptable saltthereof and the chloride channel activator compound is X:Y; wherein, Xis the parts by weight of the pesticide (I), (II), or any agriculturallyacceptable salt thereof, and the numerical range is 0<X≦20; Y is theparts by weight of the chloride channel activator compound, and thenumerical range is 0<Y≦20.
 16. The composition of claim 15, wherein theranges of weight ratios of the pesticide (I), (II), or anyagriculturally acceptable salt thereof and the chloride channelactivator compound are X₁:Y₁ to X₂:Y₂, wherein one of the followingconditions is satisfied: (a) X₁>Y₁ and X₂<Y₂; or (b) X₁>Y₁ and X₂>Y₂; or(c) X₁<Y₁ and X₂<Y₂.
 17. A method of controlling pests comprisingapplying the pesticidal composition of claim 1, near a population ofpests, in an amount sufficient to control the pests.
 18. The method ofclaim 17, wherein the chloride channel activator compound comprises anavermectins-based compound.
 19. The method of claim 17, wherein thechloride channel activator compound comprises a milbemycins-basedcompound.
 20. The method of claim 17, wherein the chloride channelactivator compound comprises at least one of abamectin, emamectinbenzoate, lepimectin, and milbemectin.
 21. The method of claim 17,wherein the chloride channel activator compound comprises emamectinbenzoate.
 22. The method of claim 17, wherein the pests comprise sapfeeding insects, chewing insects, or both.
 23. The method of claim 17,wherein the pests comprise at least one of diamondback moth, Plutellaxylostella; South American brown stink bug, Euschistus heros; andWestern plant bug, Lygus Hesperus.
 24. A method for protecting a plantfrom infestation and attack by pests, the method comprising contactingthe plant with the pesticidal composition of claim
 1. 25. The method ofclaim 24, wherein the chloride channel activator compound comprises anavermectins-based compound.
 26. The method of claim 24, wherein thechloride channel activator compound comprises a milbemycins-basedcompound.
 27. The method of claim 24, wherein the chloride channelactivator compound comprises at least one of abamectin, emamectinbenzoate, lepimectin, and milbemectin.
 28. The method of claim 24,wherein the chloride channel activator compound comprises emamectinbenzoate.